Throughout life, the dental pulp nurtures cells that are responsible for the main tenance, renewal and repair of dentin, a principal component of the tooth. The unique association between pulp and dentin begins with the development of the dental papilla. Odontoblasts maintain this intimacy through normal function, reactions to dental treatment and in repair by synthesizing new dentin. This proposal is based on the fundamental hypothesis that Transforming Growth Factor - Beta (TGF-BETA) influences odontoblast differentiation during tooth formation and in repair. TGF-BETA is implicated as a regulatory factor in the control of cell growth, differentiation and function, and it appears to be of major importance in embryogenesis and in the repair of tissue injury. In addition to promoting angiogenesis, TGF-BETA is a potent chemotactic and mitogenic agent for several types of cells, including platelets, macrophages, lymphocytes and fibroblasts. Many of the regulatory activities of TGF-BETA are a function of its ability to enhance the formation of extracellular matrix. TGF-BETA dramatically influences osteoblasts, cells highly specialized for synthesis of extracellular matrix during bone formation. Cultured osteoblasts have receptors for TGF-BETA, and also produce and secrete the factor. Odontoblasts are cells related in function to osteoblasts; they synthesize dentin extracellular matrix during tooth development and repair. The specific aims of the proposed study are: 1. To determine if TGF-BETA is present in developing rat molars, 2. To describe the relationship between the temporal and spatial patterns of TGF-BETA expression and odontoblast differentiation in developing rat molars, 3. To characterize the presence of TGF-BETA in adult human pulps, and 4. To compare TGF-BETA levels in healthy, adult human pulps with those in inflamed human pulps. Immunolocalization experiments using a polyclonal antibody preparation that recognizes TGF-BETA, will be performed on rat tooth germs in various stages of development. The results will be correlated with morphogenetic and histogenetic events known to occur at each stage of development. Human pulps from healthy and carious teeth will be subjected to immunohistochemistry and Western immunoblot analysis for TBF-BETA. Incident levels of TGF-BETA and its expression within pulp cells will be compared in the two groups. Future experiments will utilize well characterized in vitro approaches to examine the effect of TGF-BETA on the synthesis of extracellular matrix proteins in odontoblasts. The long-range goals of this research are to provide a better understanding of the mechanism of odontoblast differentiation during tooth formation, and to study the origin and nature of precursor odontoblasts in pulp during reparative dentin formation, a basic phenomenon that influences the practice of clinical operative dentistry.